Medical device, in particular for the separation of a fluid

ABSTRACT

A medical device for separating a fluid, in particular for separating platelet-rich plasma from whole blood, includes three containers and at least one corresponding connection line having an intermediate bifurcation. Provided on the connection line are valve means for enabling or preventing a flow of fluid. At least one container includes a hollow container body and a plunger associated in a movable way to the container body. The device also includes a filtering member on the connection line.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/036,640, filed on May 13, 2016, which is a 371 national stageapplication of PCT/IB2014/066015 filed Nov. 13, 2014, which claimspriority to Italian Patent Application No. TO2013A000925 filed on Nov.14, 2013, the entire disclosures of which are incorporated herein byreference.

FIELD OF THE INVENTION

The present invention relates in general to medical devices, inparticular medical devices for the treatment and/or control of fluids,such as biological liquids and tissues in the fluid state. The inventionhas been developed with particular reference to the devices that can beused for sampling a fluid from a subject, separating it into fractionsand possibly obtaining a concentrate from one of the separate fractions.In this perspective, the invention has a preferred application intreatments aimed at separating platelet-rich plasma (PRP) from wholeblood.

PRIOR ART

Devices of the type referred to are known and usually comprise at leastthree containers, constituted by pliable bag containers. In general, theblood of a patient is delivered to a collection bag, integrallyconnected in series to which are two transfer bags. After obstructingwith a clamp the connection tube between the collection bag and thefirst transfer bag, the device is set in a centrifuge in order tosubject the blood contained in the collection bag to soft spinning. Inthis way, the blood basically separates into a layer of sediment on thebottom of the collection bag, containing red and white blood cells, anda supernatant layer, containing plasma with platelets, closer to theupper part of the bag, which is provided with an outlet port. Next, theclamp is released and the collection bag is compressed in an extractordevice, for forcing the plasma containing the platelets into the firsttransfer bag so that a fraction of the blood containing prevalently thered and white blood cells will remain in the collection bag. Afterobstructing once again the connection tube of the collection bag andpossibly obstructing with a clamp the connection tube between the firstand second transfer bags, the device is once again set in a centrifugein order to subject the plasma with platelets to heavy spinning andthereby obtain a concentrate of platelets on the bottom of the firsttransfer bag and leave thereon a supernatant layer of platelet-poorplasma. With the connection tube between the two transfer bags free, thefirst transfer bag is compressed in order to transfer part of the layerof platelet-poor plasma to the second transfer bag, so that there willremain in the first transfer bag part of the plasma with the concentrateof platelets, which can be put back in suspension with a view to itssubsequent use. The use of pliable bag containers integrally connectedcomplicates handling of the device and renders difficult separation ofthe fractions of the blood in a precise way, above all when relativelysmall amounts of blood, in the region of 20-100 ml of whole blood, areto be treated.

There have also been proposed devices in which the container forcollecting the blood to be separated is constituted by a rigid containerof a syringe type, which possibly includes just one pliable transferbag. Also these devices are, however, complicated to produce andinconvenient to use.

SUMMARY AND OBJECT OF THE INVENTION

In view of what has been set forth above, the object of the presentinvention is basically to provide a device of the type referred to thatis simple and economically advantageous to produce, as well as beingreliable, safe, precise, and convenient in operation for the operatorswho have to use them.

The above and other objects still, which will emerge more clearlyhereinafter, are achieved according to the present invention by medicaldevices and methods for separating fluids, such as biological liquidsand tissues in the fluid state, which present at least thecharacteristics referred to in the annexed claims.

BRIEF DESCRIPTION OF THE DRAWINGS

Further objects, characteristics, and advantages of the invention willemerge from the ensuing description, with reference to the annexeddrawings, which are provided purely by way of non-limiting example andin which:

FIG. 1 is a schematic perspective view of a medical device according toone embodiment of the invention;

FIGS. 2 and 3 are schematic perspective views of two modules of amedical device according to one embodiment of the invention;

FIG. 4 is a perspective view of a further module of a medical deviceaccording to a preferred embodiment of the invention;

FIG. 5 is a schematic perspective view of a first container of a syringetype of a medical device according to one embodiment of the invention;

FIG. 6 is a schematic perspective view of a plunger of the container ofFIG. 5;

FIG. 7 is a schematic perspective view of a stem of the plunger of FIG.6;

FIGS. 8 and 9 are a schematic perspective view of a component of thecontainer of FIG. 5, and a corresponding detail, respectively;

FIG. 10 is a schematic perspective view of a part of a head of theplunger of FIG. 6;

FIG. 11 is a view similar to that of FIG. 6, with the component of FIG.8 associated to the plunger, in a first condition;

FIG. 12 is a schematic cross section of the container of FIG. 5, in thecondition of FIG. 11;

FIGS. 13 and 14 are views similar to those of FIGS. 11-12, in a secondcondition;

FIG. 15 is a schematic cross section, at an enlarged scale, of a portionof a medical device according to the invention;

FIGS. 16 and 17 are details of FIG. 15;

FIG. 18 is a view of a component visible in FIG. 17, in a differentoperative condition;

FIG. 19 is a schematic perspective view of an apparatus that can be usedin combination with a device according to the invention including atleast the modules of FIGS. 2 and 3;

FIG. 20 is a schematic perspective view of the apparatus of FIG. 19,with a corresponding casing removed;

FIG. 21 is a sectioned view of a portion of the apparatus of FIG. 19;

FIG. 22 is a schematic perspective view of a module of a medical deviceaccording to a variant embodiment of the invention;

FIGS. 23 and 24 are a sectioned view of a filtering member of the moduleof FIG. 22, at an enlarged scale, and a corresponding detail,respectively;

FIGS. 25, 26, and 27 are views similar to those of FIGS. 22-24,regarding a module of a medical device according to a further variantembodiment of the invention.

FIG. 28 is a view similar to that of FIG. 1, regarding a further variantof the invention; and

FIG. 29 is a detail, with a component partially sectioned, of a deviceaccording to the variant of FIG. 28.

DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION

Reference to “an embodiment” or “one embodiment” in the framework of thepresent description is intended to indicate that a particularconfiguration, structure, or characteristic described in relation to theembodiment is comprised in at least one embodiment. Hence, phrases suchas “in an embodiment” or “in one embodiment” and the like that may bepresent in various points of this description do not necessarily referto one and the same embodiment. Furthermore, particular conformations,structures, or characteristics defined in the framework of the presentdescription may be combined in any adequate way in one or moreembodiments, which may also differ from the ones represented. Numericalreferences and spatial references (such as “top”, “bottom”, “upper”,“lower”, etc.) used herein are only provided for convenience and hencedo not define the sphere of protection or the scope of the embodiments.Furthermore, in the present description and in the attached claims, theterm “treatment”, when it refers to a fluid, is to be understood in itsbroadest sense, and as used herein is intended to comprise activities,such as sampling of a biological or medical fluid, as well as processingthereof, for example for separating it into its fractions and/orconcentrating a separated fraction thereof.

The term “fluid” is to be understood in its broadest sense, and as usedherein is intended to comprise biological or medical fluids or liquids,in particular fluids or liquids comprising particles that may be atleast in part separated and/or concentrated, such as cells or plateletsor fragments of cells, preferably particles which contain growthfactors, cytokines, and bioactive molecules. Preferably, the fluid isblood and/or its components, i.e., a biological fluid basically made upof a corpuscular part typically comprising red blood cells, white bloodcells, and platelets, and a fluid part constituted by plasma.

In the figures the same reference numbers are used to designate elementsthat are similar or technically equivalent to one another.

In its more general terms, a medical device according to the invention,or a corresponding module, comprises at least one from among thefollowing:

-   -   at least one container provided with a plunger with removable        stem;    -   at least two containers provided with a corresponding plunger,        each belonging to a corresponding module;    -   at least one bag container;    -   at least one needle for sampling a fluid, preferably a pair of        needles;    -   at least one connection line, in particular one including a        tube;    -   at least one hydraulic-connection attachment or connector;    -   at least one self-operating valve;    -   at least one valve designed to prevent any contamination of the        fluid from outside following upon separation between two        modules;    -   at least one releasable attachment or connector having        associated thereto a self-operating valve;    -   at least one from among a deviator valve, a shutoff valve, and a        tap;    -   at least one filter, such as a separation filter and/or an        anti-bacterial filter and/or a leukocyte filter;    -   at least one tangential-filtration filter, in particular for        concentrating a platelet-rich plasma, and/or a filter designed        to provide a protection, such as an anti-bacterial filter;    -   at least one identification element and/or one memory element,        preferably of a wireless or radiofrequency type; and    -   a plurality of modules that can be separated during different        steps of use of the device.

A possible embodiment of a medical device for separating a fluid isrepresented schematically by way of example in FIG. 1, the device beingdesignated as a whole by 1. In what follows, it is to be assumed thatthe fluid considered is whole blood and that the device 1 is used forseparation of platelet-rich plasma, for example for regenerativeapplications and/or for physiological renewal and/or tissue repair inspecialist clinical sectors, such as orthopaedics, plastic surgery, andmaxillo-facial surgery.

The device according to the invention preferentially comprisesdisposable components provided in sterile packaging. Very preferably,the device comprises all the components necessary for taking a bloodsample from a patient, preventing coagulation of the blood, separatingthe sample into its fractions, and obtaining a concentrated fraction. Inmore general terms, the device enables treatment of a fluid in a closedsystem, i.e., in conditions such as to prevent any contamination of thefluid itself from outside during the various operating steps.

In the example illustrated, the device 1 comprises a container 10 forreceiving the fluid to be treated, here whole blood, a container 20 forreceiving a first fraction of the fluid, and a container 30 forreceiving a second fraction of the fluid. As will emerge clearlyhereinafter, the container 10 is a container for centrifuging the fluid,suitable for being set in a centrifuge. In a preferred, but notexclusive, embodiment, also at least one other between the container 20and the container 30 may be a container suitable for being set in acentrifuge in order to subject a fraction of the starting fluid tocentrifuging.

The three containers each have a first port for fluid inlet and/or fluidoutlet, designated, respectively, by 10 a, 20 a and 30 a, to which therecan be associated the ends of a hydraulic connection line, comprising,for example, one or more transparent pliable tubes. In greater detail,the aforesaid line, designated as a whole by 40, includes a first linebranch 40 a, with a first inlet end that can be associated to the port10 a of the container 10 and at least one intermediate bifurcation 41,comprising, for example, a wye or tee, so as to define at least onesecond line branch 40 b and one third line branch 40 c. The branches 40b and 40 each define an outlet end of the line 40, which can beassociated to the ports 20 a and 30 a of the containers 20 and 30,respectively. Preferentially, operative on the connection line 40 arevalve means, such as shutoff valve means or flow-deviator valve means,designated as a whole by 42, which can be operated for enabling orpreventing a flow of fluid through the branch 40 b and/or the branch 40c.

According to a characteristic of the invention, the device 1 has amodular structure; i.e., it comprises a plurality of stages or modulesthat are connected together in a separable way, for enabling separationaccording to the operating step of use of the device 1.

Preferably, the device 1 envisages an initial configuration in which allthe modules provided, for example two or three modules, are associatedto one another and sterilized, in particular for defining a device inwhich the inside of all the components—such as containers of the fluidand/or fractions thereof, as well as corresponding connection lines andvalve means—is sterile and protected from any contamination fromoutside, enabling maintenance of a condition of sterility of the fluidand of its separated or concentrated fractions during the variousoperating steps of use of the device 1.

The aforesaid modules include at least one first module, designated as awhole by A, which comprises the container 10 and a corresponding portion(40 a) of the line 40, and a second module, designated as a whole by B,which comprises at least one between the container 20 and the container30, with a corresponding portion (40 b and/or 40 c) of the line 40. In apreferred embodiment, such as the one represented, the module B includesboth of the containers 20 and 30 with the corresponding line branches 40b and 40 c, but not excluded from the scope of the invention is the casewhere the container 20 and the branch 40 b, on one side, and thecontainer 30 and the branch 40 c, on the other, belong to two differentmodules of the modular structure.

According to a further characteristic of the invention, provided atleast at the interface between two modules of the modular structure ofthe device 1 are hydraulic connectors, in particular of the typecomprising at least two parts that can be coupled together mechanicallyin a fluid-tight way, designed to provide both a hydraulic connectionbetween the modules, enabling passage of the fluid, and a mechanicalconnection between the modules to enable easy handing of the device 1.Preferably, the connectors are of the separable or releasable type, inparticular for enabling convenient separation between the modules inquestion.

With reference to the example represented, designated by 43 is such areleasable connector, operatively set between the modules A and B.

Preferentially, the connector 43 is provided upstream of the bifurcation41 and downstream of the valve means 42, but in various embodiments (notillustrated) there may be provided two distinct releasable connectorsset downstream of the bifurcation 41, in addition or as an alternativeto the connector 43, each on a corresponding branch 40 b and 40 c of theline 40. As will emerge clearly hereinafter, the releasable connectorsprovided are preferentially formed by two parts or attachments that canbe coupled together, each of which belongs to a corresponding module ofthe device 1, the connectors being preferably of a screw or threadedtype, even though they may be of some other fast-engagement and/orfast-release type.

The container 10 is preferably a container having a rigid structure andmay possibly be used for direct sampling of the fluid to be subjected totreatment and/or of a corresponding auxiliary substance: in this case,the container 10 may be a container of a syringe type, which may beequipped with a corresponding sampling needle. However, in a preferredembodiment of the invention, the device 1 comprises at least one furtherconnection line, designated as a whole by 50, for setting in fluidcommunication the connection line 40, in particular its first branch 40a, with at least one between a first sampling device 55 for sampling thefluid and a second sampling device 56 for sampling an auxiliarysubstance of the process. In the case exemplified herein, where thedevice 1 is used for separating whole blood, the first sampling device55 fluid is a needle or cannula for venous sampling, whereas the secondsampling device 56 can be a needle, for sampling an anti-coagulant froma container not belonging to the device 1. In a different embodiment,the second device 56 fluid is constituted directly by a container of theauxiliary substance.

One or both of the aforesaid sampling devices 55 and 56 may possiblybelong to the module A, with the corresponding connection line 50connected to the connection line 40. However, in a particularlypreferred embodiment of the invention, at least one of the samplingdevices 55 and 56 belongs to a further module of the structure of thedevice 1 that is different from the modules A and B. In the examplerepresented, the aforesaid further module is designated by C andcomprises both of the sampling devices 55 and 56. In the embodimentexemplified, where both of the sampling devices 55 and 56 are provided,the connection line 50 includes an outlet branch 50 a, for connection tothe first branch 40 a of the first connection line 40, as well as twoinlet branches 50 b and 50 c, which are each connected to a respectivesampling device 55, 56 and converge into the outlet branch 50 a. Also,preferably provided at the interface between the modules A and C is areleasable connector 44, for example of the same type as the connector43.

Preferentially, the device 1 comprises one or more self-operatingvalves, including self-closing valves, which can be at least in partintegrated in a corresponding hydraulic connector for connection betweentwo modules, or else operatively set in the proximity of the aforesaidconnector.

In a preferred embodiment, for example, at least one self-operatingvalve 45 is provided, configured for enabling a flow from the branch 40a to the branch 40 b and/or 40 c and for preventing any reflux from thebranch 40 b and/or from the branch 40 c of the line 40 to thecorresponding branch 40 a and/or for automatically closing the passagetowards the branches 40 b and/or 40 c preventing any contamination fromoutside in the case of separation of the parts of the connector 43. Aswill be seen, such a valve may be integrated in a part of the connector43, on the branch 40 a upstream of the bifurcation 41 and downstream ofthe valve means 42. In one embodiment, such as the one exemplified, thevalve means 42 belong to the module A, whereas the valve 45 belongs tothe module B.

In the case where the module C is provided, or in any case at least onesampling device 55 and/or 56 is provided, a self-operating valve may beprovided for enabling a flow from the line 50 to the line 40 andpreventing any reflux from the line 40 to the line 50 and/or forautomatically closing the passage towards the line 40 and/or container10 preventing any contamination from outside in the case of separationof the parts of the connector 44. Preferentially, but not necessarily,the aforesaid self-operating valve—not indicated in FIG. 1 in so far asit is integrated in the attachment or connector designated by 48—isprovided substantially in an interface area between the branch 40 a ofthe line 40 and the branch 50 a of the line 50. As will be seen, in oneembodiment, this self-operating valve belongs to the module A.

The self-operating valve or valves envisaged by the device 1 mayadvantageously be configured as one-way or non-return valves, orpossibly deviator valves or shutoff valves.

One or more modules of the structure of the device 1 may also compriseat least one further shutoff member on at least one branch of acorresponding connection line 40 or 50, such as, for example, one ormore clamp valves, some of which are designated by 47 a, 47 b and 47 cand hereinafter defined for simplicity as “clamps”.

Represented in FIG. 2 is an embodiment of the module A, basicallyconstituted by a disposable sterile set, comprising the container 10,preferably having a rigid structure, and a corresponding part of theconnection line 40, in particular its branch 40 a, and the valve means42.

The branch 40 a preferentially comprises a pliable tube 40 a′, forexample made of PVC or other elastomer. The tube 40 a′ may indicativelyhave an internal diameter of 2.8 mm, an external diameter of 4 mm, and alength of approximately 60 mm.

The valve means 42 preferentially comprise a shutoff valve or a tap, inparticular of a mechanical type, namely with a manually operated and/ormechanically operated control element, without any electricalconnection. In the embodiment exemplified, the above valve is a deviatorvalve, here constituted by a three-way tap, with corresponding knob orcontrol element 42 a. In the example, one of the three ways is closedwith a plug, and in alternative embodiments (not represented) the valvein question may be a valve or tap with just two ways (an inlet and anoutlet), of an open or closed type.

One way 42 b of the tap 42 is in fluid communication, via the tube 40a′, with the port 10 a of the container 10. For this purpose, the inletend of the tube 40 a′ is provided with an attachment 48, configured forcoupling with a corresponding attachment 11 b of the container 10defining the port 10 a. In one embodiment, the coupling between theattachments 48 and 11 b is of a fast type, preferably of a Luer type. Onthe other hand not excluded are other types of coupling (a screwcoupling, a bayonet coupling, a snap-in coupling, etc.).

A second way 42 c of the tap 42 is closed by a plug 42 d, whilst theremaining way 42 e of the tap includes or has associated thereto a part43 a of the hydraulic connector 43 of FIG. 1, which is preferentially athreaded connector. In the example, the ways 42 c and 42 e of the tap 42are provided for this purpose with a thread, preferably of a male type.

In the case where the device 1 according to the invention comprises themodule C, the attachment 48 may be a three-way connector, such as a tee,in order to enable connection of the line 50, in particular of itsbranch 50 a (FIG. 1), to the line 40, in particular to its branch 40 a.In the example represented, the attachment 48 also defines a part 44 aof the hydraulic connector 44 of FIG. 1, which is also preferentially athreaded connector, preferably of a male type. As explained hereinafter,on the other hand, in a different embodiment, the module C could beconnected to the way 42 c of the tap 42.

As has been said, in one embodiment, at least one self-operating valveof the device 1 is integrated at least in part in a hydraulic connectoror attachment. Preferentially, such a self-operating valve comprises anopen/close element and a resilient element, such as a spring, preferablya helical spring. The resilient element that determines automaticclosing of the open/close element preferably has a predefined orcalibrated force, for example to prevent movement of the open/closeelement in the presence of values of pressure different from thepredefined ones (such as a valve that does not open with values ofnegative pressure on one side of the open/close element and/or ofpositive pressure on the opposite side that are higher than a predefinedvalue).

The self-operating valve, preferably a fast-operating valve, can performthe function of shutting off or automatically deviating the flows duringcertain steps of use of the device 1, or automatically closing a line ofa part or module of the device, in particular for preventing any leakageof fluid and/or contamination from outside. The self-closing device orvalve is preferably of a fast type.

For instance, in FIG. 2 a self-operating valve (described hereinafter)is integrated in the attachment 48, and specifically in its part 44 a.As explained hereinafter, on the other hand, such a valve may beomitted, in configurations of the device 1 different from the oneillustrated (or possibly replaced by a valve designed to closeautomatically upon detachment of the part 44 b of the connector 44).

Represented in FIG. 3 is a possible embodiment of the module B, which isalso basically constituted by a disposable sterile set, comprising thecontainers 20 and 30, the corresponding parts of the connection line 40,in particular its branches 40 b, 40 c with the bifurcation 41, a part 43b of the connector 43, preferably with a threaded attachment, and aself-operating valve 45. In a preferred embodiment, such as the onerepresented, the container 20 is a container of a syringe type, hencewith a rigid structure, comprising a generally elongated container bodyor barrel, designated by 21, and a plunger, designated by 22, which isassociated in a movable way to the barrel 21. The plunger 22 includes aplunger stem and a plunger head, here not represented but designated by22 a and 22 b in FIG. 15, which are fixed with respect to one another.The container 20 may be a commonly used disposable syringe, for examplewith a capacity of 20 or 30 ml, but in possible variant embodiments thecontainer 20 may be of the same type described hereinafter as thecontainer 10, i.e., of the type in which the head and the stem of theplunger are coupled in a separable way. At its distal end the barrel 21has an attachment 23, preferably a fast attachment, for example of aLuer type, defining the port 20 a.

The container 30 is preferentially a generally pliable and/orcompressible container, in particular a bag container, for example witha capacity of 30 or 60 ml, made, for example, of polymeric plasticmaterial, such as EVA, or an elastomer. Preferentially, associated tothe port 30 a of the container 30 is a connector 31, for example a wyehaving an area 31 a that can be perforated with a needle, such as amembrane made of elastomer.

The branches 40 b and 40 c preferentially comprise respective pliabletubes 40 b′ and 40 c′, in particular of the same type and dimensions incross section as the tube 40 a′. The tubes 40 b′ and 40 c′, which mayindicatively have a length of 60 and 80 mm, respectively, each have afirst end connected to a respective way of the connector defining thebifurcation 41. The second end of the tube 40 b′ is provided with anattachment 24, configured for coupling with the attachment 23 definingthe port 20 a. Preferentially, the coupling between the attachments 23and 24 is of a Luer type, even though other types of coupling (a screwcoupling, a bayonet coupling, a snap-in coupling, etc.) are notexcluded. The second end of the tube 40 c′ is instead connected to theconnector 31 associated to the port 30 a of the container 30.

Associated, either directly or with interposition of a correspondingtube, to the connector defining the bifurcation 41, on the opposite sidewith respect to the tubes 40 b′ and 40 b′, are the connector 43 and theself-operating valve 45. Preferentially, the body of the valve 45 isshaped, on the side opposite to the bifurcation 41, for providing arespective part 43 b of the hydraulic connector 43, which is to coupleto the part 43 a associated to or defined by the tap 42 (FIG. 2).

In one embodiment, on at least one of the branches 40 b and 40 c, inparticular downstream of the bifurcation 41, at least one shutoff memberis provided. Such a case is exemplified in FIG. 3, where designated by47 a is a clamp on the branch 40 b. In a different embodiment, the clamp47 a may be on the branch 40 c or on both of the branches. The presenceof the clamp 47 a, albeit preferable for practical reasons, is not to beunderstood as essential, given that it may possibly be replaced by othershutoff means or by a self-operating valve.

Represented in FIG. 4 is a possible embodiment of the module C, which isalso basically constituted by a disposable sterile set. In the example,the module C comprises sampling devices 55 and 56 and the connection way50.

The device 55 is here constituted by a needle preferably provided withtabs 55 a for fastening to the patient from whom the blood sample is tobe taken. Likewise, the device 56 comprises a further needle, forsampling an anti-coagulant or other auxiliary substance from a containernot belonging to the device 1. In possible variants, as alreadymentioned, the device 56 may consist of a container for theanti-coagulant or other auxiliary substance.

The branches 50 b and 50 c of the connection line 50 comprise pliabletubes 50 b′ and 50 c′, preferably made of polymeric or elastomericmaterial, such as silicone or PVC, for example with a length of 300 and80 mm, respectively, the ends of which opposite to the needles areconnected to the inlet ways of an intermediate connector 49, inparticular a three-way tee or wye. The branch 50 a of the line 50 alsocomprises a tube 50 a′, preferably of the same type as the ones used forproviding the line 40, for example 60 mm long. The first end of the tube50 a′ is connected to the outlet way of the connector 49, whilstassociated to its second end is a corresponding part 44 b of thehydraulic connector 44 of FIG. 1, for coupling with the part 44 a ofFIG. 2. As has been said, the coupling is preferably of a threaded type.

In a preferred embodiment, provided on at least one of the branches 50 band 50 c, in particular upstream of the connector 49, is a shutoff flowmember: illustrated in FIG. 4 is the case where both of the branchesreferred to are provided with clamps similar to the clamp 47 a,designated by 47 b and 47 c, respectively.

In one embodiment of the invention, the container 10 of FIG. 2 is shapedsubstantially as a syringe for injection and/or fluid sampling, and assuch comprises a generally elongated container body or barrel,designated by 11, and a plunger, designated by 12, associated in amovable way to the barrel 11.

In general terms, the plunger 12 has a plunger head (not represented inFIG. 2) that is slidably engaged in a fluid-tight way within barrel 11,for defining thereby a chamber for collecting the fluid that is incommunication with the port 10 a. Connected to the plunger head is aplunger stem 13, which can be displaced in the barrel 11 for moving theplunger head, and thereby varying the volume of the collection chamberfor introducing the fluid therein or expelling it therefrom,respectively. The stem 13 is connected in a releasable way to theplunger head via a coupling arrangement that comprises first couplingmeans, at a distal end of the stem, and second coupling means, on a faceof the plunger head that is opposite to the first end of the containerbody.

The aforesaid coupling arrangement may be of any type known in thesector, for example with a bayonet coupling, a threaded coupling or, ingeneral, an arrangement in which coupling and decoupling between thestem and the head is obtained via angular movements of the former withrespect to the latter. However, in a preferred embodiment of theinvention, the aforesaid arrangement is obtained according to theItalian patent application entitled “Medical device for the treatment offluids”, filed on the same date by the present applicant, the teachingsof which are incorporated herein for reference. In brief, according tothe solution proposed by the present applicant, the container 10comprises a maneuvering shaft 14, which is slidably mounted on theplunger stem 13 and can be operated manually for causing disengagementbetween the aforesaid first and second coupling means, and if need befacilitating their mutual engagement.

Preferentially, the aforesaid coupling means may be engaged to oneanother and disengaged from one another in a way at least in partelastic. Once again preferably, the stem 13 and the shaft 14 aresubstantially coaxial.

A possible embodiment of the container 10, which may, for example, havea capacity of 60 ml, is illustrated in FIGS. 5-14.

With reference to FIG. 5, the barrel 11 has an end wall 11 a providedwith the attachment 11 b. The opposite end of the barrel 11 has a secondport (not represented) for insertion and sliding of the plunger 12. Inone embodiment, substantially at the aforesaid second port, the barrel11 has a flange 11 c projecting outwards for facilitating manualgripping of the container 10 and/or its anchorage to anautomated-treatment apparatus (here not represented). With reference toFIG. 6, the plunger 12 comprises, at its distal end, a plunger head 15for slidable engagement in a fluid-tight way in the barrel 11, fordefining therewith a chamber for collecting the fluid, which is incommunication with the port 10 a. The plunger 12 includes the plungerstem 13, which is connected to the head 15 and can be displaced formoving the head itself and thereby varying the volume of the aforesaidcollection chamber, in order to admit or expel the fluid, respectively,as in a syringe. In one embodiment, the plunger head 15 comprises a capor core 15′ made of relatively rigid material and a coating part made ofgenerally elastic material, which forms a gasket 15″, designed toguarantee the necessary seal of the head 15 with respect to the innersurface of the barrel.

In the preferred embodiment, the stem 13 is connected in a releasableway to the head 15, via a coupling arrangement that comprises firstcoupling means, at a distal end of the stem 13, and second couplingmeans, on a face of the head 15 that is opposite to the port 10 a. Thestem 13 is shaped so as to define a seat 16, within which the shaft 14is axially slidable from an inoperative position to an operativeposition, for causing disengagement between the aforesaid first andsecond coupling means. If need be, the shaft 14 may also be made toslide from the inoperative position to the operative position, in orderto cause or facilitate mutual engagement between the aforesaid couplingmeans.

Visible in FIG. 7 is the distal end of the stem 13, here designated as awhole by 13 a. In one embodiment, the aforesaid first coupling meansinclude a plurality of elastically deformable coupling or engagementelements, in particular at least two coupling elements, preferablyopposed to one another, it being, however, possible for a singlecoupling element to be provided. With reference to the exampleillustrated, these coupling elements basically comprise two opposedpairs of tabs 17, at the distal end 13 a of the stem 13. According toembodiments (not represented), at the bottom end of the stem 13 just twoopposed tabs 17 could be provided or, in the limit, even just oneelastically deformable tab 17, on just one side of the stem. In theexample, each tab 17 has, on its innerside, an engagement relief ortooth 17 a, which preferentially extends in a transverse direction overthe tab.

The maneuvering shaft 14 (visible in FIGS. 8-9) has a control portion 14a and an actuation portion 14 b shaped for interacting with the tab ortabs 17. For this purpose, in one embodiment, the portion 14 b comprisesat least one inclined plane, configured for interacting with at leastone surface of a corresponding tab 17 of the stem 13, in particular arelief thereof 17 a. With reference to the example represented, as maybe clearly seen in FIG. 9, the end surface of the portion 14 b isdistinguished by the presence of two inclined planes 14 c that areopposed and divergent towards the end 14 a of the shaft 14, each ofthese inclined planes being radiused to a generally plane surface 14 d.In the example, the surfaces 14 d are substantially parallel.

The second coupling means provided on the plunger head 15 comprise atleast one second coupling element, with respect to which an aforesaidfirst coupling element (here represented by a tab 17 of the stem 13) canbe engaged/disengaged. Visible in FIG. 10 is a possible embodiment ofthe plunger head, and in particular of its core 15′, which preferablyhas a generally circular shape. In the example, the core has asubstantially disk-shaped main wall 15 b, from the upper face of whichthere rise two pairs of radial walls 15 c and 15 d, which define acentral space 15 e between them. Provided at the upper end of at leastone wall 15 d is at least one respective second coupling or engagementelement 18. The element 18 preferentially comprises, at least onepart—such as a step or an engagement element and/or an inclinedplane—configured for interacting with a surface of a corresponding firstcoupling element (i.e., a tab 17, in the example). In the example ofFIG. 10 two elements 18 are provided, the upper ends of which aredistinguished by the presence of two inclined planes 18 a opposed anddivergent towards the wall 15 b, each of which is radiused to a surfacethat is generally transverse or perpendicular to the wall 15 d so as todefine a respective step or engagement 18 b.

FIGS. 11-12 illustrate the condition where the head 15 is coupled to thestem 13 of the plunger 12. It should be noted that, merely for a moreconvenient understanding, in FIG. 12, the head 15 is represented in theposition of maximum advance. In this condition, the reliefs 17 a of thetabs 17 (for their part external to the space 15 e of FIG. 10) engagewith the steps 18 b of the coupling elements 18, with the tabs 17substantially straight or in a predefined position, i.e., substantiallynot subjected to elastic stress. In the coupled condition, with orwithout the maneuvering shaft 14, the container 10 can be used as asyringe, for the purposes of sampling a fluid through the port 10 adefined by the attachment 11 b.

In the case where it becomes necessary to separate the stem 13 from thehead 15, for example for putting just the barrel 11 in a centrifuge, theshaft 14 is to be pushed towards the inoperative position of FIGS. 13-14(which are similar to FIGS. 11-12, but represent a condition ofdecoupling between the stem and the head). The thrust exerted on theshaft 14, while the stem 13 is withheld, causes application of a forceon the tabs 17, and in particular on the part of their teeth or reliefs17 a. The “wedge-shaped” portion defined by the inclined planes 14 c(FIG. 9) of the actuation portion 14 b of the shaft 14 penetratesprogressively between the reliefs 17 a of the pairs of opposed tabs 17(for their part facing the space 15 e), causing elastic divarication ofthe tabs themselves, as may be seen in FIGS. 13-14. After extraction ofthe stem 13 with the shaft 14, the barrel 11 can be processed asrequired, for example by putting it into a centrifuge (after obstructingthe port defined by the attachment 11 b or the tube associated to theattachment).

Visible in FIG. 15 is a portion of the device 1 of FIG. 1, at anenlarged scale and sectioned, whereas visible in FIGS. 16 and 17 areenlarged details of FIG. 15. From these figures, and in particular fromFIG. 16, there may be noted a possible embodiment of the attachment 48,set between the tube 40 a′ and the attachment 11 b of the container 10,where the lateral way or branching way of this attachment obtains thepart 44 a of the hydraulic connector 44. As has been mentionedpreviously, in a preferred embodiment, the attachment 48 or theconnector 44 integrates or has associated a self-operating valve, aimedat preventing any possible reflux from the tube 40 a′ to the tube 50 a′and/or any contamination from outside upon detachment of the connectorpart 44 b.

In the example represented, present within the body of the attachment 48(or of the connector 44) is an open/close element 48 a, which iselastically forced into closing of the way internal to the part 44 a,for example via a spring 48 b or other elastic element. In the presenceof a flow with suitable pressure coming from the tube 50 a′, theopen/close element 48 a can recede by overcoming the elastic reaction ofthe spring 48 b. Instead, in the absence of a flow from the tube 50 a′,the spring 48 b keeps the open/close element 48 a in a position forclosing the way internal to the part 44 a of the connector 44.Preferentially, the force of the spring 48 b and the mass of theopen/close element 44 a are predefined in such a way as to keep theopen/close element 48 a in a closing position also during thecentrifuging steps (in other words, hence, the force of the spring issuch as to overcome the force exerted by the mass of the open/closeelement in the centrifuging step). Preferably, the open/close system 48a-48 b is shaped in such a way that, in the presence of a flow from theport 10 a of the container 10 towards the tube 40 a′, the pressure ofthe fluid contributes to maintaining the system itself in its closingposition, illustrated in FIGS. 15 and 16.

From FIG. 17 it may be appreciated how, in the embodiment illustrated,the embodiment of the self-operating valve 45 is basically similar tothat of the valve 48 a-48 b just described above, the teachings of whichmay thus be considered as referring also to the valve 45. In this case,the spring 45 b of the valve 45 tends to keep the correspondingopen/close element 45 a in a position for closing the line branch 40 a,upstream of the bifurcation 41, whereas in the presence of a flow withsuitable pressure from the branch 40 a towards the bifurcation, theopen/close element 45 a can recede countering the action of the spring45 b. Preferably, also in this case, the force of the spring 45 b andthe mass of the open/close element 45 a are predefined in such a way asto keep the open/close element 48 a in a closing position also duringthe centrifuging steps. Also in this case, the open/close element 45 ais preferentially shaped in such a way that, in the presence of apossible flow in the opposite direction (from the line branch 40 cand/or 40 b towards the line branch 40 a), the pressure of the fluidcontributes to keeping the open/close element itself in its closingposition, illustrated in FIG. 17.

The structure illustrated for the valve 45 and/or 48 a-48 b, heresubstantially a one-way valve or a non-return valve, is to be understoodmerely as an example, given that such valves may have any structuresuitable for the purpose, for example with an open/close systemconstituted by an elastically deformable membrane designed to open andclose a port of passage or provided at the centre with a port of passagedesigned to open elastically when the membrane is forced by a flow or apressure in one direction and to close elastically when the flow orpressure ceases, or else close when the membrane is forced by a flow ora pressure from an opposite direction. Such a membrane is preferablymade of elastomer and/or its elasticity is such as to obtain functionssimilar to those of the spring 44 b, 45 b described previously.

Once again visible in FIG. 17 is the tap 42, within which an open/closeelement 42 f operates, which can be turned by means of the controlelement 42 a. In the example, as has been said, the tap 42 is athree-way tap, with the open/close element 42 f that defines a teechannel. In a first angular position of the open/close element 42 f(FIG. 17), the passage of fluid between the ways 42 b and 42 e isprevented, whereas in a second angular position of the open/closeelement (illustrated in FIG. 18) this passage is allowed. It should benoted, on the other hand, that also with the open/close element 42 fturned through 90° in a clockwise direction with respect to FIG. 18 orin a counterclockwise direction with respect to FIG. 17, passage offluid is allowed between the ways 42 b and 42 e. As has already beenmentioned, the tap 42—which itself forms a part of the connection line40—can also be replaced by a valve or tap with just two ways, of anopen/close type.

In a possible variant embodiment, the line 50 of the module C, andspecifically its connector part 44 b, can be coupled in a differentposition on the line 40, once again upstream of the open/close means 42f of the tap 42, and in particular of the way 42 c of the tap, insteadof the plug 42 d. In this case, the valve 48 a-48 b integrated in theattachment 48 or in the connector 44 may possibly be associated to thetap 42 or be omitted and its functions be performed by the tap 42. Insuch a case, with the open/close element 42 f turned through 90° in acounterclockwise direction with respect to FIG. 18, the ways 42 b and 42c will be in fluid communication, whereas the way 42 e will be occluded,thus enabling passage of the blood and/or of the anti-coagulant into thecontainer 10. Instead, with the open/close element 42 f turned through90° in a clockwise direction with respect to FIG. 18, it will be theways 42 b and 42 e that are in fluid communication, whereas the way 42 cwill be occluded in order to enable flow from the container 10 towardsthe bifurcation 41. To an angular position of the open/close element 42f corresponding to that of FIG. 17 there will correspond, instead,closing of the way 42 b, with the ways 42 c and 42 e in communicationwith one another. Such a position may be selected, for example, when thecontainer 10 is to be handled, after the blood and/or the anti-coagulanthave been loaded therein and the module C has been removed from thedevice.

A possible methodology of use of a device described for the purposes ofseparation of platelet-rich plasma from whole blood and concentrationthereof is described hereinafter. It is to be assumed, for this purpose,that the device 1 is supplied already assembled, or else is assembled inthe condition represented in FIG. 1 at the moment of use, preferably insterile environment.

The clamp 47 b provided on the branch 50 b of the line 50 is operative(in the condition for closing the tube 50 b′) and, preferentially, thetap 42 is in the position of FIG. 17, i.e., a position that occludes theline 40 downstream of the attachment 48; the clamp 47 c provided on thebranch 50 c of the line 50 is, instead, inoperative (in the condition ofopening of the tube 50 c′). The plunger 12 of the container 10 is madeto recede, as in an ordinary syringe, for sampling from an externalcontainer or flask, via the needle 56, a certain amount ofanti-coagulant, for example 5 ml which can be preferentially detectedvia a graduated scale present on the barrel 11 of the container 10. Theclamp 47 c is then brought into its operative condition, and the clamp47 b is brought into its inoperative condition. Via the needle 55 bloodsamples are taken from a subject, such as a person or animal, gettingthe plunger 12 of the container 10 to recede further.

As a variant, a sample can be taken from a container containing blood orfluid previously taken from a subject, possibly already added withanti-coagulant. In this case, the module C of the device 1 may notcomprise the needle 56 and the corresponding line 50 c and the connector49, with a single line 50 instead of the lines 50 a and 50 b. When acertain amount of blood, for example 50 ml that can be detected via theaforesaid graduated scale, has been allowed to enter the container 10,retraction of the plunger 12 of the container 10 is stopped, and theclamp 47 b is preferably brought into its operative condition. The orderof the operations for sampling the anti-coagulant and the blood maypossibly be reversed.

At this point, by releasing the hydraulic connector 44, the module C canbe removed from the device 1, for example to enable disposal thereof,with the valve 48 a-48 b that closes and isolates the line 40automatically.

The stem 13 of the corresponding plunger 12 is removed from thecontainer 10, for example with the modalities exemplified previously.The module A, preferably connected with the module B, is put in acentrifuge in order to cause a first separation between parts of thewhole-blood/anti-coagulant mixture contained in the container 10, inparticular to obtain a sedimentation in at least two layers, onecomprising plasma with platelets and the other comprising red and whiteblood cells, as a result of their different density or different weight.In this way, in the variable-volume chamber of the container 10 therewill be present a layer of sediment comprising red and white blood cellsand a supernatant layer comprising plasma and platelets, with a volumeapproximately in relationship to the haematocrit of the patient. Thedevice 1 is positioned in the centrifuge in such a way that, followingupon centrifuging, the layer of sediment will be closer to the head 15of the plunger 12, whereas the supernatant layer will be comprisedbetween the layer of sediment and the wall 11 a of the barrel 11provided with the attachment 11 b. Preferentially, the separation of theplasma and of the platelets from the red and white blood cells isobtained with a centrifuging with low acceleration (indicatively 150-350g, for example 260 g) for a time comprised between 8 and 15 min, forexample 10.5 min, with an initial, acceleration, ramp of 30 s, and afinal, deceleration, ramp of approximately 3 min. The module A, with themodule B, if associated thereto, is taken out of the centrifuge, keepingthe container 10 in a vertical position and preventing any agitationthereof.

With the modules A and B connected, the tap 42 is brought into theposition of FIG. 18, i.e., in a position that sets the ways 42 b and 42e in communication, and the clamp 47 a is brought into its operativecondition, for closing the branch 40 b of the line 40. It should benoted that the position illustrated in FIG. 1 for the clamp 47 a ispurely explanatory, since it could be in a position very close to thebifurcation 41.

By operating the plunger 12 or the plunger head 15 there is a transferof part of the contents from the container 10 to the bag container 30(or, as will be seen, to the container of a syringe type 20). Inparticular, the plunger 12 and/or its head 15 are/is made to advance soas to transfer just the supernatant layer, i.e., plasma with platelets,or a portion thereof, from the container 10 to the bag container 30. Inthis step, the valve 48 a-48 b integrated in the attachment 48 preventsexit of the plasma from the connector part 44 a, while the valve 45 isopened by the thrust or pressure exerted by the blood on the open/closeelement 45 a.

The aforesaid advance can be obtained manually or else, preferentially,with the aid of suitable automated equipment: in the former case, thecontainer 10 must be provided once again with the corresponding plungerstem 13; in the latter case, the automated equipment—a possibleembodiment of which will be described hereinafter—may be conceived so asto operate directly the head 15 of the plunger 12 of the container 10,in which case it is not necessary to re-install beforehand thecorresponding stem 13. After transfer of the plasma with platelets intothe bag container 30, the module A can be removed by separating the twoparts of the hydraulic connector 43. Any possible exit of the plasmafrom the module B is prevented thanks to the presence of the valve 45,which also prevents any contamination from outside.

The module C is then put in the centrifuge, with the bag container in asubstantially vertical position and with the corresponding port 30 a setat the top, this positioning being enabled by the pliability of thetubes 40 b′, 40 c′. The centrifuging carried out on the bag container 30is more energetic than the previous one; i.e., it is a centrifuging withhigh acceleration, preferably in the region of 1000-1500 g for a timecomprised between 6 and 15 min, for example 1200 g for 8 min. In thisway, a concentration of the plasma with platelets is obtained; i.e.,there is obtained, once again by sedimentation, a further separationthereof into a platelet-rich fraction and a platelet-poor fraction. Inparticular, a platelet-poor fraction remains uniformly suspended in thebag container 30, whereas a fraction with high concentration ofplatelets is found on the bottom of the bag, in a position opposite tothe port 30 a.

The clamp 47 a is then brought into its inoperative condition foropening the tube 40 b′. The plunger 22 of the container of a syringetype 20 is pulled back to draw in from the bag container 30 theplatelet-poor plasma, in amounts depending upon the level ofconcentration that is to be obtained in the bag 30. It should be notedthat, during operation of the plunger 22 of the container 20, air is notdrawn in from the valve 45 in so far as the latter has a structure suchas to exert a closing force greater than the negative pressure or forcenecessary for intake.

A possible value of platelet-poor plasma drawn in is approximately 10ml, corresponding to 10 ml of plasma remaining in the bag together withthe platelets. The total value of plasma of approximately 20 ml isobviously indicative and depends upon the patient being treated.Preferably, in any case, in the bag container 30 there remains a part ofplatelet-poor plasma and the platelet concentrate.

At this point, the bag container 30 can be rubbed gently in order tobring about disaggregation of the platelet concentrate previouslysedimented by centrifuging. The product is then ready for being used:for this purpose, it is possible to sample the concentrate obtained, forexample from the point of injection 31 a of the connector 31 by means ofa further syringe provided with a needle.

In a possible variant, the clamp 47 a is provided on the branch 40 c ofthe line 40, and the functions between the containers 20 and 30 arereversed. In such a case, after centrifuging carried out on thecontainer 10 and with the clamp 47 a set in the operative condition forclosing the branch 40 c, the plasma with platelets is transferred fromthe container 10 to the container of a syringe type 20, and, afterremoval of the module A, the module B can be put into the centrifuge. Insuch an embodiment, the container 20 can also have a structure similarto that of the container 10, i.e., have a plunger stem that can beseparated from the corresponding plunger head. With the more energeticcentrifuging carried out on the contents of the container 20 separationof the plasma is obtained into a platelet-rich fraction and aplatelet-poor fraction. Positioning of the container 20 in thecentrifuge will be such that the fraction richer in platelets will becloser to the head 22 a of the corresponding plunger 22 and theplatelet-poor fraction will be located between the enriched layer andthe end of the container 20 having the port 20 a.

After removal of the module B from the centrifuge, the clamp 47 a isbrought into its inoperative condition. The plunger 22 of the container20 is then operated for expelling from the container itself at leastpart of the platelet-poor fraction, which flows into the bag container30. In this way, within the container 20 there remains prevalently theplatelet-rich fraction, for subsequent use or further treatmentaccording to the specific protocol followed. The container 20 withplatelet-rich plasma may also be separated from the rest of the module Bfor purposes of convenient use.

Also in this case, operation of the plunger 22 of the container of asyringe type 20 can be carried out manually or using automatedequipment: in the latter case, as has been said, the container 20 mayhave a structure such as to enable separation between the stem and thehead of the corresponding plunger.

In the previous examples, there has been hypothesized a prevalentlymanual use of the device 1 but, as has been mentioned, one or more stepscould be carried out with the aid of automated equipment, for example byautomatically controlling forward operation of the plunger head 15 ofthe container 10 and/or operation of the tap 42 and/or detection of thevariation between the supernatant layer, comprising plasma andplatelets, and the sediment layer, comprising red and white blood cells.

In its more general terms, a medical system or apparatus according tothe invention, preferably automated and/or for use in combination with amedical device, preferably a device for separating a fluid, such as adevice 1 of the type described previously, comprises one or more fromamong the following:

-   -   means for controlling an automated displacement of at least one        between a plunger stem and a plunger head of a container of the        medical device;    -   means for controlling an automated displacement of a control        element of a valve means of the medical device;    -   detection means for detecting a characteristic of a flow present        within a fluidic connection line of the medical device;    -   electromagnetic or optical sensor means, preferably comprising        at least one emitter and at least one receiver of        electromagnetic radiation;    -   supporting means for a container of the medical device,        preferably configured for keeping said container in a generally        vertical position;    -   a member for actuation of one from among a plunger stem, a        plunger head, and a container of the medical device and means        for controlling displacement of the actuation member;    -   sensor means for detecting the position of an actuation member        with respect to a plunger head of a container of the medical        device;    -   a stationary support for an electromagnetic or optical sensor        system, the support preferably including, substantially in a        position corresponding to the optical sensor system, a        positioning seat for a stretch of a connection line of the        medical device;    -   a support for a valve means of the medical device;    -   an electromagnetic or optical sensor system including two        electromagnetic or optical sensors in sequence or in series with        respect to one another;    -   a support associated to which is an element provided with means        shaped for positioning a stretch of a connection line of the        medical device in a position corresponding to a sensor system of        the apparatus, in particular within a corresponding seat;    -   a system for actuating a valve means of the medical device,        preferably comprising a movable member shaped for coupling to a        control element of the aforesaid valve means; and    -   means for reading and/or for unidirectional or bidirectional        communication of data with an identification element of the        medical device.

A possible embodiment of an automated equipment is representedschematically by way of example in FIGS. 19-21, where it is designatedas a whole by 60, and in which the modules A and B of the device 1described previously are highlighted.

The apparatus 60 has a load-bearing structure or body 61, preferablyprovided with a stationary support 62 for housing and/or positioning thecontainer 10. In the example, the aforesaid support 62 is located at thefront and configured for setting the container 10 in a verticalposition, i.e., with the port 10 a and attachment 11 b upwards. In theexample, the support includes a slot or seat 62 a for receiving theflange 11 c (FIG. 5) of the barrel 11 of the container 10, from whichthe corresponding stem 13 has previously been removed. Movable within ahollow part of the support 62 is an actuation member 63 a designed tomove the plunger head 15 of the container 10 in a controlled way. As maybe seen in FIG. 20, the actuation member 63 a belongs to a structure 63that is vertically movable in opposite directions with respect to a base61 a and is driven via an actuator 64. The actuator 64 may for examplebe an electric motor with screw-operated shaft 64 a, associated towhich—for example via an auger—is the structure 63, so that the lattercan be displaced vertically in a guided way. In the example, thestructure has a part configured substantially like a slide, coupled to acorresponding vertical guide 63 b.

The position of the structure 63, and hence of the actuation member 63a, may be controlled via suitable sensors forming part of the controlsystem of the apparatus, designated as a whole by 65. One of the sensorsreferred to above, for example a proximity sensor or a microswitch, isdesignated by 66.

The control system 65, the program or software of which monitors generaloperation of the apparatus 60, includes suitable control means, forexample a programmable logic circuit (PLC), and user-interface means,for example a display 65 a of a touch-screen type, for setting thecommands and required operating parameters.

Preferentially, the apparatus 60 also includes a support 67 (FIG. 19)for an electromagnetic or optical sensor system, preferably a sensor oftransparency or opacity, and/or shutoff or deviation valves or means.

The above sensor system, designated by 68 in FIGS. 20 and 21, includesat least one emitter and at least one receiver of electromagneticradiation, for example light radiation. Provided in one embodiment is anemitter of a signal with a predefined wavelength and a receiver designedto detect the aforesaid signal and/or its variations. Preferentially,the sensor system is conceived for transmitting the electromagnetic orlight signal through a stretch of a line or tube of the device 1 that istransparent to the aforesaid signal, where the latter varies at thereceiver end (for example, it is attenuated or in any case altered) as afunction of the composition of the flow passing through the tube. Forinstance, passage of a greater amount or concentration of givensubstances or particles in the fluid (such as red and/or white bloodcells) in the stretch of tube set between the transmitter and thereceiver prevents or attenuates passage of the signal between thetransmitter and the receiver, with the aforesaid variation of signalthat is thus indicative of the composition of the flow passing through.

Alternatively, the sensor system 68 is conceived for transmitting anelectromagnetic or light signal that at least in part undergoesdeviation or refraction owing to the presence of substances or particlesin the fluid. As in the previous case, passage of a differentcomposition or greater amount or concentration of given substances orparticles in the fluid in the aforesaid stretch of tube causes adifferent refraction of the signal that can be detected at the receiverend, indicating, for example, transition between plasma and red or whiteblood cells.

The sensor system may also be prearranged for detecting the colouring ofthe flow passing through the tube, for example on the basis of detectionof the absorption of light by substances or particles present in thefluid.

The support 67 is shaped so as to define a passage or seat 67 a(represented dashed in FIG. 19 in so far as it is covered by a removablelid 67 b), where there can be inserted a stretch of the tube 40 a′ (or,if need be, of the tube 40 b′, in the case where the container of asyringe type 20 is replaced by a container similar to the container 10and it is intended to automate the final step of the separation method,preferably according to the variant described previously).

In a position corresponding to the aforesaid seat 67 a, preferablymounted on sides set at an angle with respect to one another or oppositeto one another, are the aforesaid emitter (for example, a light-emittingdiode or LED) and receiver (for example, a photoresistance or aphototransistor). Preferably, two optical sensors are provided insequence or in series with respect to one another, such as a pair ofemitters in sequence and a pair of corresponding receivers in sequence,designated by 68 a and 68 b in FIG. 21. Preferentially, the lid 67 b isshaped in such a way as to push and/or position a corresponding stretchof the tube 40 a′ or 40 b′ in a correct position within the seat 67 a,in a position corresponding to the sensor system 60. For this purpose,the side of the lid facing the seat for the lid 67 b is preferablyprovided with an appropriately shaped internal relief, designated as awhole by 67 c in FIG. 19.

The distance between the emitters, on one side, and the receivers, onthe other, i.e., the distance between two optical sensors in sequence,may for example be approximately 10 mm.

Preferentially, the support 67 integrating the optical sensor system isshaped also for defining means for supporting or positioning the tap 42,designated as a whole by 67 d in FIGS. 19 and 21, or else a supportindependent of the support 67 may be provided for this purpose.Preferentially, the supporting means 67 d are configured for coupling atleast in part with the shape of the body of the tap 42, and/or parts ofthe device 1 close to the tap, in particular in order to support itand/or keep it in position during operations performed on the tapitself, such as movement of its control element 42 a.

With reference once again to FIG. 21, operative within the actuationmember 63 a, and in particular in a position corresponding to its upperend, is a sensor 69, for example a microswitch, used by the system 65for controlling the position of the member 63. In particular, the sensor69 has the function of detecting the mechanical contact between the topof the member 63 a and the plunger head 15 of the container 10 when themember 63 a is raised via the corresponding actuation system.

In an advantageous embodiment, a further actuation system is alsoprovided, controlled by the control system 65 of the apparatus 60, forcontrolling, in an automated way, switching of the tap 42 between atleast some of the positions described previously.

For this purpose, the control element 42 a of the tap 42 can be shapedfor coupling to a corresponding actuation member, preferably providedwith a seat having a shape at least in part complementary to that of thecontrol element. A further actuation system of this sort is exemplifiedin FIG. 21, where designated by 77 is a rotatable member, to which therecan be coupled the control element 42 a of the tap 42, which is operatedvia an actuator (not represented), such as an angularly movable actuatoror an electric motor with rotatable shaft. The rotatable member 77preferentially has a seat or impression 77 a designed to receive thecontrol element 42 a at least partially, i.e., at least to the extentwhere it is possible to impose a rotation thereon. In the example, thisseat 77 a is set low down and is in part complementary to the controlmember 42 a of the tap 42, which is preferably provided with radiallobes and/or is shaped so as to be operable both manually and in anautomated way.

Other shapes useful for the purpose for obtaining rotation of thecontrol element 42 a via the rotatable member 77 are evidently possible.The control element 42 a and the seat 77 a could have other mutuallycomplementary or coupleable shapes, for example of a polygonal type(triangular, square, pentagonal, etc.) or star-shaped type, or complexshapes comprising linear stretches and/or curved stretches.

Preferentially, at the start of an operating cycle of the apparatus, themember 77 has an angular position such that the control element 42 a ofthe tap can be coupled in the seat 77 a only when the tap itself is in apredefined position, for example the position of FIG. 18, or in any casea position such that the open/close element 42 f sets the ways 42 b and42 e in communication (it is not on the other hand excluded that theaforesaid predefined position corresponds to the condition for closingthe passages between the ways 42 b and 42 e, as for example in FIG. 17).

According to an operative example, after the container 10 has beencoupled to the support 62, and after—via the user interface 65 a—theparameters possibly requested have been entered and a command for startof cycle has been imparted, the actuator 64 moves the structure 63 frombelow upwards, for example starting from a lowered end-of-travelposition (not represented). In the case where the predefined position ofthe tap were the closing position, for example as in FIG. 17, the system65 previously issues a command for rotation of the member 77 in order tobring the tap itself into the opening position, for example that of FIG.18. At a certain point of rising of the structure 63, the control system65 detects, via the sensor 69, contact between the member 63 a and theplunger head 15, in this way acquiring information regarding theposition of the head itself. Detection of this position may, forexample, be useful for enabling first a relatively fast advance of themember 63 a and then a slower movement thereof, following upon contactbetween the head 15 and the member 63 a. The sensor 69 hence enablesdetection of the position of effective start of travel or thrust on theplunger head 15, and thus automatic detection of the effective travel ordistance of movement of the head itself.

After contact, the member 63 a then starts to bring about displacementof the head 15, which itself may be controlled at different speeds, forexample with an faster initial step and a slower final step (such as aninitial speed of displacement of the head 15 of 2 mm/s for a distance of8 mm and then a speed of 0.05 mm/s up to conclusion of the cycle).During movement of the plunger head 15, the flow within the line branch40 a is intercepted by the optical system 68, in particular so as tomeasure the transmittance or other optical characteristic of the fluidthat is passing, preferably in two points of the tube 40 a′ set at adistance from one another (in a way corresponding to the distancebetween two sensors 68, such as the distance existing between theemitters 68 a and the receivers 68 b of each pair). Preferentially, thecontrol electronics carries out automatic calibration with respect tothe value detected by the optical system upon turning-on of theapparatus 60, before and/or after positioning of the device 1 on theapparatus. When the plasma starts to rise as a result of the thrustexerted by the member 63 a on the plunger head 15, the optical system 68detects a first variation of the optical characteristic considered (forexample, the transmittance), corresponding to the air-plasma transitionin the branch 40 a, and a second variation of the same opticalcharacteristic when the red and/or white blood cells pass, i.e., uponpassage of plasma-blood cells in the branch 40 a. The control system 65then interrupts operation of the motor 64, and hence of the member 63 a,when both of the receivers 68 b of the system have detected the presenceof red and/or white blood cells. Sampling of the signal may for examplebe carried out at a frequency of approximately 1 kHz, which correspondsto a displacement of the fluid of approximately 50 μm between onesampling and the next.

Furthermore, when the control system 65 detects, via the optical sensor68, the aforesaid second variation of the optical characteristicconsidered, indicating the start of flow of the reject part (containingthe red and white blood cells), also the actuator associated to themember 77 is operated so as to turn the control element 42 a of the tap42 to bring its open/close element into the position of FIG. 17 or inany case into a position such as to prevent any flow between the ways 42b and 42 e.

The system is programmed so as to convey into the bag container 30 theplasma and the platelets and leave instead the red and white blood cellsin the module A, i.e., in the container 10 and in the correspondingbranch of the connection way 40. For the purpose of complete recovery ofall the platelet-enriched plasma there may be predefined an appropriatedelay or further travel, between the moment of optical detection and themoment of interruption of the movement of the actuation member 63 a andactuation of the member 77. For instance, with a container 10, having anaverage diameter of 29.2 mm, after optical detection, the plunger risesonce again by 0.57 mm, corresponding to a distance traversed in the tube40 a′ (internal diameter of 2.8 mm) of 62.1 mm, recovering a volume ofplasma of 381.9 mm³.

In one embodiment, the medical device forming the subject of theinvention comprises at least one filtering member, preferably forultrafiltration, for example on at least one branch of the firstconnection line 40. Filtration is preferably of a tangential type andbased upon the use of filtering elements that will enable thecorpuscular part of the plasma (i.e., the platelets and growth factorsthat may be present in the plasma) to be withheld in the line 40 andwill separate part of the liquid fraction thereof, principallyconstituted by water. Preferentially, an aforesaid filtering member—thatmay include one or more porous membranes—belongs to the module B.

An embodiment in this sense is exemplified in FIG. 22, where designatedas a whole by 70 is a filtering member operatively set on the branch 40b of the connection line 40. As will be seen, a filtering member can beset on the branch 40 c or, possibly, each branch 40 b, 40 c can beprovided with a respective filtering member.

Illustrated in cross-sectional view in FIG. 23 is the member 70,prearranged for carrying out a filtration substantially of a tangentialtype, via a plurality of hollow porous fibres, some of which aredesignated by 71, substantially shaped like small tubes with porouscylindrical walls. The active part of the member 70 may include between30 and 100 hollow fibres, preferably 40-60 fibres, with a lengthcomprised between 40 and 80 mm, preferably 50 mm. The internal diameterof the hollow fibres is indicatively comprised between 100 and 500 μm,preferably 250 μm. The hollow fibres preferably have porosity with asize comprised between 5 and 15 kdalton, very preferably 7 kdalton, orcomprised between 1 and 5 nm, so as to withhold the platelets but alsopossible growth factors present in the plasma.

The member 70 includes a casing body 72, in the cavity of which twotransverse walls 72′ define a central collection chamber 70 a and twoterminal connection chambers 70 b, each facing an axial end wall of thebody 72 that is provided with a respective duct or attachment 73 a, 73 bfor connection along the line branch 40 b. The fibres 71 have respectivethrough portions in the walls 72′ in order to keep the fibres themselvesin position substantially like a bundle. In this way, the open ends ofthe fibres 71 are located within the connection chambers 70 b providedwith the ducts 73, 73 b, as may be clearly seen in FIG. 24, where thepores of some fibres are highlighted. The intermediate and prevalentpart of the fibres 71 extends instead within the collection chamber 70 asubstantially in an axial direction. As may be inferred, via the ducts73 a, 73 b, the filtering member 70 is connected in series between twostretches of the line 40 b, whilst the fibres 71 connect the terminalchambers 70 b in parallel to one another. The chamber 70 a is designedto collect a discarded liquid fraction of the plasma, in particularrepresented by water containing molecules below the size of porosity ofthe fibres 71. Preferentially, the chamber 70 a has at least one passage70 a′ (FIG. 22) provided with a valve or an appropriate membrane (of aGoreTex® type) that is permeable to air but not to liquids in order toenable the air to exit when the aforesaid discarded liquid fractionenters the chamber 70 a.

The module B of FIG. 22, which may have characteristics in common to themodule B described previously, can be coupled, for example, to themodule A in order to obtain a device according to the invention, inparticular so as to include valve means designed to enable or prevent aflow of fluid through the branches 40 a, 40 b and 40 c of the connectionline 40. These valve means may comprise, for example, the tap 42 (herenot represented), and the clamp 47 a, which is here on the branch 40 c,and the self-operating valve 45.

In general, the aforesaid valve means may assume a first operativecondition, in which a flow of fluid along the line 40 between thecontainer 10 and the container 30 (or the container 20, as has beenexplained) is allowed, and a second operative condition, in which a flowof fluid along the line 40 between the container 30 and the container20, or vice versa, is allowed.

The use of a filtering member enables, if so required, omission of thesecond step of plasma centrifuging envisaged by the methodologiesdescribed previously. In particular, after the plasma with platelets hasbeen transferred from the container 10 to the container 30, for examplewith the modalities already described previously, it is possible to getthe plasma itself to pass one or more times through the filtering member70 by operating the plunger 22 of the container of a syringe type 20,also in opposite directions, with the valve means represented by theclamp 47 a in the respective condition that enables passage of theplasma between the containers 30 and 20. For instance, in the case whererepeated passages through the member 70 are to be carried out, theplunger 22 can be operated in one direction to draw in the plasma withplatelets from the container 30 to the container 20, and then beoperated in the opposite direction, in order to force the residue ofplasma with platelets from the container 20 to the container 30, and soforth (alternatively, as has been explained, the plasma with plateletscan be initially delivered to the container 20 instead of to thecontainer 30, in which case the order of actuation of the plunger 22will be reversed with respect to what has just been indicated).

At each passage through the filtering member 70 the plasma passes firstinto a chamber 70 b, then through the hollow fibres 71, and then intothe other chamber 70 b. In the passage through the fibres 71, the plasmaloses water and small molecules through the corresponding pores, with afiltration of a tangential type, preferably minimizing the contact ofthe platelets with the porous cylindrical wall of the fibres 71 andpreventing both loss of a part thereof owing to adhesion on the internalsurfaces of the fibres and their possible activation caused bymechanical stress.

For the aforesaid contact not to occur, or for it to be as limited aspossible, it is preferable for the flow within the member 70 to be of alaminar type: in this way, the particles, in particular the platelets,tend to concentrate where the speed of the fluid is greater, namelyalong the axis of symmetry of the fibres 71.

The waste liquid that traverses the pores of the intermediate part ofthe fibres 71 reaches the collection chamber 70 a, whilst the remainingpart of the liquid fraction, in which the concentration of platelets isincreased, can proceed until it reaches the container 20 (or, in thecase of a further cycle, the container 30, with reverse operation of theplunger 22). In this way, it is possible obtain the desiredconcentration of platelet-enriched plasma. These cycles of concentrationor movement of the plunger 22, which may be carried out manually orautomatically via an apparatus, can terminate with the residue ofplatelet-rich plasma in the bag container 30, which enables a moreconvenient storage at a low temperature and a transport in conditions ofsterility, or else in the container of a syringe type 20, which enablesa more immediate use.

The porous membranes or hollow fibres used in the application proposedcan be obtained with purposely designed materials, for examplepolyvinylidene fluoride (PVDF), polyether sulphone (PES), polypropylene(PP), polyethylene (PE), polysulphone (PS), polyacrylonitrile (PAN),polyvinyl chloride (PVC), polyamide (PA), polyarylether sulphone (PAES),polyvinyl pyrrolidone (PVP), or mixtures thereof.

A different embodiment is exemplified in FIG. 25, where the filteringmember, here designated by 70′, is operatively set on the branch 40 c ofthe connection line 40. As for the previous case, on the other hand, themember 70′ may be set on the branch 40 b or, possibly, each branch 40 b,40 c may be provided with a respective filtering member. It is alsopossible to provide one member 70 on a branch and one member 70′ on theother branch.

FIG. 26 is a cross-sectional view of the member 70′, which in this caseis prearranged for carrying out a filtration substantially of atangential type via a plane porous membrane, designated by 71′. Themember 70′ includes a casing body 72, preferably made up of at least twoparts 72 a and 72 b that can be coupled together in a fluid-tight way,with the filtering membrane 71′ set in between.

The part 72 a is provided with corresponding ducts 73 a, 73 b forconnection along the branch 40 c, which are preferably angled ducts, forexample L-shaped ducts, so as to have a corresponding proximal endfacing the membrane 71′. The part 72 b defines the collection chamber 70a for collecting the discarded liquid fraction of the plasma, whichextends underneath the membrane 71. Also in this case, the member 70′has at least one passage 70 a′ provided with an appropriate valve ormembrane for enabling the waste fraction to reach the collection chamber70 a.

Irrespective of the specific embodiment of the casing body 72, it ispreferably shaped so as to define a gap, which extends substantiallyparallel to the membrane 71′, on the side opposite to the collectionchamber 70 a. The gap extends between the proximal ends of the ducts 73a, 73 b and the membrane itself, preferably obtaining a chamber with anextensive surface but with a reduced height, in particular in order forthe membrane to be lapped better by the fluid. A possible embodiment ofsuch a gap is designated by 74 in FIG. 27, where some pores of themembrane 71′, designated by 71 a, are also highlighted.

Operation of a device according to the invention integrating the moduleB of FIGS. 25-27 is similar to what has been described above withreference to FIGS. 22-24. Also in this case, with the clamp 47 a in thecondition of opening (here on the branch 40 b) it is possible to get theplasma to pass one or more times through the filtering member 70′ byoperating the plunger 22 of the container of a syringe type 20. At eachpassage through the filtering member 70′, the plasma passes through thegap 74, lapping the membrane 71′ with a preferably laminar flow. Part ofits liquid fraction penetrates into the pores 71 a of the membrane 71′to reach the collection chamber 70 a, whereas the remaining part of theliquid fraction, where the concentration of platelets is increased, canproceed until it reaches the container 20 (or, in the case of a furthercycle, the container 30, with reverse operation of the plunger 22), asfor the embodiment of FIGS. 22-24, in order to obtain the desiredconcentration of platelet-enriched plasma.

Also for the application referred to in FIGS. 25-27 purposely designedmembranes can be used, preferably made of a material of the typereferred to previously and/or with filtering characteristics similar tothe hollow fibres already referred to or with a porosity designed towithhold preferably molecules above 7 kdalton, for example, membranesfor nanofiltration and reverse osmosis of the type generally used forhaemoconcentration processes.

A filtering member, in particular with anti-bacterial functions, canalso be provided along the connection line of one of the samplingdevices 55, 56, in particular the device 56, also in addition to one ormore filters provided on the line 40. For instance, as illustrated inFIGS. 28 and 29, an anti-bacterial filter 80 may be set between thedevice 56 and the connector 49, or more in general downstream of thedevice 56. In such an embodiment, operative within the body of thefilter 80 are one or more membranes 81 with pores sized so as to allowflow of the liquid—here the anti-coagulant—and withhold, instead,possible bacteria.

FIGS. 28 and 29 highlight clamp valves 47 b′ and 47 c′ on the branches50 b and 50 c of the line 50, which have a structure different from theones previously designated by 47 b and 47 c, but perform similarfunctions. Similar clamps can be used on the modules A and/or B also inthe previous embodiments.

In one embodiment, such as the one exemplified in FIG. 28, on the branch40 a there may be present a further clamp 47, in particular located inthe proximity of the attachment 48, for enabling closing of the branch40 a towards the tap 42 during sampling of a fluid (blood and/oranti-coagulant) via the module C and/or during centrifuging of themodule A. Use of such a clamp 47 has the purpose of preventingundesirable passage of the fluid along the branch 40 a. After samplingof the fluid or centrifuging, the clamp 47 is brought into a positionfor opening the branch 40 a. A similar clamp can be provided also in theembodiments described previously.

From the foregoing description, the characteristics of the presentinvention emerge clearly, as likewise do its advantages, which areprincipally represented by the simplicity of embodiment of thedisposable medical device proposed, by its contained cost, by itsprecision and simplicity of use and handling, and by its safety.

The modular construction of the device is advantageous also in relationto the possibility of combining together modules having differentcharacteristics, according to the requirements of use. For instance, itis possible to envisage modules or stages C differentiated from oneanother as regards type or size of the needle so that they adapt betterto the characteristics of the patient (adult or child), or once againmodules or stages A and B differentiated on the basis of the subjectand/or the type of fluid to be treated or separated, for example with adifferent bag or a container of a syringe type, or with differentvolumes, or with the possible addition of other devices.

The modularity referred to is particularly useful in the steps ofproduction of the device, enabling manufacture and warehousing of thevarious separate modules, which can be assembled on the basis of thespecific requirements of the clientele. The modularity of the device 1avoids the need to stock devices 1 in multiple complete configurations;i.e., it enables warehousing of the various separate modules, to beassembled rapidly if need be, with a reduction of the costs of storageand a faster production and/or delivery to the customer. The modules Aand/or B and/or C can be produced separately, assembled together toproduce a device 1, sterilized and packaged for subsequent use.

Also the methodologies of separation and concentration proposed, as wellas the corresponding equipment, prove advantageous as regards theirsimplicity of implementation, effectiveness, and precision.

Particularly advantageous is the possibility of separating the modulesof the device, without any risk of contamination of the fluid by theexternal environment, in particular considering the fact that theshutoff-valve means or means for automatic closing of the ducts arepreferably set in the proximity of the hydraulic connectors or insidethem. The possibility of separation between the modules moreover enablesa more convenient handling of the device during its steps of use.

It is clear for the person skilled in the art that numerous variationsmay be made to the devices and to the methods described by way ofexample herein, without thereby departing from the scope of theinvention as defined by the annexed claims.

A filter having a structure similar to that of the filter 80, provided,however, with a membrane 81 designed withhold the leukocytes, could beprovided on at least one of the branches 40 b, 40 c of the module B,preferably in series to the filter 70, 70′ described previously, whensuch a filter 70, 70′ is envisaged.

Among the possible variants, the possibility may here be mentioned ofproviding a separation device including substantially just twocontainers, which can preferably be connected together via a lineprovided with a filtering member of the type designated previously by 70or 70′, for example the containers 10 and 30, or else 10 and 20, or onceagain the containers 20 and 30, at least one of which is possibly of acentrifugable type, in order to carry out a separation of a fluid intoat least two fractions, in particular according to the methodologydescribed previously.

The self-operating valve or valves used in the device do not necessarilyhave to be integrated in respective attachments or connectors, but canbe operatively arranged in the proximity of the aforesaid connectors, ona corresponding line branch or tube.

The modules A and/or B and/or C or their parts can be combined togetherin a way and/or in a number different from what has been illustrated anddescribed herein, for providing variants of the device according to theinvention.

According to a preferential variant of the invention (not represented),the device 1 envisages at least one identification element, for examplean identification element containing data. Such an element may, forexample, be a barcode or else an electronic identification device,preferably of a wireless type (for example, a radiofrequency or RFIDdevice), designed to transmit and/or receive data. In such anembodiment, the apparatus 60 is preferably provided with means fordetecting and/or transmitting data to the aforesaid identificationelement (for example, an optical sensor or a radiofrequency receivingand/or transmitting device).

Preferentially, the identification element is integrated or associatedto at least one part or a module of the device 1, preferably associatedto a container thereof, such as for example a bag container (30) or acontainer of a syringe type (10, 20). For instance, an element of anRFID type can be integrated or mounted in the barrel or in the plungerof a container of a syringe type, in particular in a protected areathereof and/or an area not subject to contact with the fluid.

In the case of an identification element of an electronic type, this ispreferably provided with memory means, for example for storinginformation regarding at least one from among the type of the device 1,the fluid sampled, and the data that can be detected by the controlsystem 65 of the apparatus 60. Information of this type can be used, forexample, for the purposes of automatic setting of operations or controlsmade by the apparatus (for example, for certifying the correctcombination of the device 1 to the apparatus 60 and/or for controllingoperation of the apparatus 60 on the basis of the fluid contained in thedevice 1 and/or for automatic configuration of at least part of theoperations and/or detections that can be made by the apparatus 60). Theidentification element may also be designed to store data regarding atleast one subject involved in the treatment of the fluid (for example,the subject from whom the blood sample has been taken and/or the subjectwho is to receive the platelet-enriched plasma).

In a possible variant (not represented), the apparatus 60 is prearrangedso as to enable operation of the plunger stem of the container 10,instead of just its head 15. In such an embodiment, then, aftercentrifuging has been carried out on the container 10, the latter mustonce again be provided with the corresponding stem 13, which is thuscoupled to the corresponding head 15. In this case, the actuationmember, previously designated by 63 a, of the apparatus 60 is replacedby a different element, designed to couple the stem 13 in its outer partto the barrel 11. For this purpose, for example, the stem 13 can beprovided with a transverse seat or cavity (designated by 13 b only inFIGS. 5-7), preferably a through seat. The seat 13 b is located inparticular in a proximal end region of the plunger stem, preferably insuch a way that at least one part of the seat itself is located in aportion of the stem 13 that is once again on the outside of the barrel11.

In such a variant, the apparatus 60 may be prearranged for carrying outalso retraction of the plunger 12 of the container 10, for example forthe purposes of automated sampling of the anti-coagulant or of the bloodand/or for intake or sampling of parts or fractions of the blood.

For this purpose, the actuation member can be prearranged for couplingto a proximal end of the plunger 12, for example configured as asubstantially fork-shaped transverse member, with an upper part thereofdesigned to penetrate into the seat 13 b and a lower part thereof thatis, instead, underneath the proximal end of the plunger 13. A may beinferred, with such a conformation, the actuation member, whentranslated upwards or downwards, brings about advance or retraction ofthe stem 13, respectively, and hence of the plunger head 15. With anembodiment of this sort, when the container 20 has a structure similarto that of the container 10 or has in any case a plunger designed tocouple to a corresponding actuation member of the apparatus 60, it ispossible to automate, using the apparatus, also the methodology offiltering with repeated passages described previously with reference toFIGS. 22-24 and 25-27. It should be noted, on the other hand, thatimplementation of this methodology using the apparatus 60 does notnecessarily presuppose that the containers 10 and 20 have the samestructure. What counts, in fact, is that the actuation member of theapparatus 60 is configured for coupling to the plunger of the container20 so as to be able to cause both advance and retraction thereof.

It is also possible to configure the apparatus 60 in such a way as tokeep the plunger or the plunger head of the container of a syringe type10 and/or 20 in a stationary position, moving, instead, thecorresponding barrel 11 and/or 21 in an axial direction (for example,rendering the part of the support 63 of FIG. 19 that integrates the seat62 a) displaceable.

As explained previously, the devices and/or systems and/or equipmentand/or the methods according to the invention find preferred applicationfor separation and concentration of platelet-rich plasma from wholeblood, but it will be appreciated that they can be used also in othermedical branches, preferably in all those medical branches in which itis useful to carry out separation and/or concentration and/or control ofliquids and/or fractions of biological liquids, tissues in the fluidstate, or liquid medical substances.

The invention claimed is:
 1. A medical device for separating a fluid,comprising: a first container for receiving the fluid to be separated, asecond container for receiving a first fraction of the fluid, and athird container for receiving a second fraction of the fluid, thecontainers each having a first port or opening for fluid inlet and/orfluid outlet; a first connection line having a first line branch with afirst end associatable to the first port of the first container, and atleast one intermediate bifurcation for defining at least one second linebranch and one third line branch with respective second ends of thefirst connection line, the second ends of the first connection linebeing associatable to the first port of the second container and to thefirst port of the third container, respectively; valve means on thefirst connection line, operable for enabling or preventing a flow offluid through at least one of the first line branch, the second linebranch or the third line branch, wherein the first container and atleast one of the second container or the third container each comprise:a hollow container body having an elongated shape with a first end and asecond end, the container body having the respective first port at thefirst end and a second port at the second end; a plunger, which isassociated in a movable way to the container body and has a plunger headthat is slidably engaged in a fluid-tight way within the container bodyfor defining thereby a fluid-collection chamber that is in communicationwith the first port, the plunger having a plunger stem that can bedisplaced in two opposite directions through the second port of thecontainer body for varying the position of the plunger head and therebyvarying the volume of the fluid-collection chamber; and at least onefiltering member on at least one of the second branch or the thirdbranch of the first connection line, wherein the plunger of the one ofthe second container or the third container is operable in a firstdirection, for inducing a flow of fluid from the second container to thethird container, and/or is operable in a second direction, opposite tothe first direction, for inducing a flow of fluid from the thirdcontainer to the second container, and thereby causing one or morepassages of the flow of fluid through the at least one filtering memberfor carrying out a separation between at least two fractions of thefluid.
 2. The medical device according to claim 1, wherein the at leastone filtering member is set on the second branch of the first connectionline.
 3. The medical device according to claim 1, wherein the at leastone filtering member is set on the third branch of the first connectionline.
 4. The medical device according to claim 1, wherein the at leastone filtering member includes a plurality of porous fibres.
 5. Themedical device according to claim 1, wherein the at least one filteringmember includes at least one porous membrane.
 6. The medical deviceaccording to claim 5, wherein the at least one filtering member includesat least one ultrafiltration membrane.
 7. The medical device accordingto claim 1, wherein the at least one filtering member includes atangential filter.
 8. The medical device according to claim 1, whereinthe at least one filtering member comprises an anti-bacterial filter ora leukocyte filter.
 9. The medical device according to claim 1, whereinthe device has a modular structure comprising a plurality of modules,connected together in a separable way, for enabling separation thereofaccording to an operating step of use of the device.
 10. The medicaldevice according to claim 9, wherein, at an interface between twomodules of the modular structure, releasable connectors are provided,each comprising at least two mutually coupling connector parts, eachconnector part belonging to a corresponding module.
 11. The medicaldevice according to claim 10, comprising at least one self-operatingvalve operatively associated to one said releasable connector, the atleast one self-operating valve being configured for preventing at leastone of the following: any contamination from outside of the fluid orfractions thereof following upon separation between two modules; anyreflux between two different branches of a connection line or betweentwo connection lines.
 12. The medical device according to claim 9,wherein the modular structure includes a third module that comprises atleast one fluid-sampling device including a device for sampling thefluid to be separated and/or a device for sampling an auxiliarysubstance.
 13. The medical device according to claim 9, wherein at leastone of the modules of the modular structure further comprises at leastone respective shutoff member on a branch of a corresponding connectionline.
 14. A system for separating a fluid, comprising a medical devicefor separating platelet-rich plasma from whole blood and an automatedapparatus; said medical device comprising: a first container forreceiving the fluid to be separated, a second container for receiving afirst fraction of the fluid, and a third container for receiving asecond fraction of the fluid, the containers each having a first port oropening for fluid inlet and/or fluid outlet; a first connection linehaving a first line branch with a first end associatable to the firstport of the first container, and at least one intermediate bifurcationfor defining at least one second line branch and one third line branchwith respective second ends of the first connection line, the secondends of the first connection line being associatable to the first portof the second container and to the first port of the third container,respectively; valve means on the first connection line, operable forenabling or preventing a flow of fluid through at least one of the firstline branch, the second line branch or the third line branch, whereinthe first container and at least one of the second container or thethird container each comprise: a hollow container body having anelongated shape with a first end and a second end, the container bodyhaving the respective first port at the first end and a second port atthe second end; a plunger, which is associated in a movable way to thecontainer body and has a plunger head that is slidably engaged in afluid-tight way within the container body for defining thereby afluid-collection chamber that is in communication with the first port,the plunger having a plunger stem that can be displaced in two oppositedirections through the second port of the container body for varying theposition of the plunger head and thereby varying the volume of thefluid-collection chamber; and at least one filtering member on at leastone of the second branch or the third branch of the first connectionline, wherein the plunger of the one of the second container or thethird container is operable in a first direction, for inducing a flow offluid from the second container to the third container, and/or isoperable in a second direction, opposite to the first direction, forinducing a flow of fluid from the third container to the secondcontainer, and thereby causing one or more passages of the flow of fluidthrough the at least one filtering member for carrying out a separationbetween at least two fractions of the fluid; said automated apparatuscomprising at least one from among: means for controlling an automateddisplacement of the plunger stem and/or the plunger head of the firstcontainer or of the at least one of the second container or the thirdcontainer of the medical device; means for controlling an automateddisplacement of a control element of said valve means of the medicaldevice; detection means for detecting a characteristic of a flow presentwithin the first connection line of the medical device; electromagneticor optical sensor means, comprising at least one emitter and at leastone receiver of electromagnetic radiation; supporting means for keepingone from among the first container, the second container or the thirdcontainer of the medical device in a generally vertical position; anactuation member for actuating the plunger stem and/or the plunger headof the first container or of the at least one of the second container orthe third container of the medical device, and means for controllingdisplacement of the actuation member; sensor means for detecting aposition of an actuation member of the automated apparatus with respectto the plunger head of the first container or of the at least one of thesecond container or the third container of the medical device; astationary support for an electromagnetic or optical sensor system, thesupport including a positioning seat for a portion of a connection lineof the medical device; a support for said valve means of the medicaldevice; an electromagnetic or optical sensor system including twoelectromagnetic or optical sensors in sequence or in series with respectto one another; a system for actuating valve means of the medicaldevice, comprising a movable member shaped for coupling to a controlelement of said valve means; means for reading data and/or forunidirectional or bidirectional communication of data with anidentification element of the medical device.